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J. Biol. Chem., Vol. 279, Issue 30, 31041-31049, July 23, 2004

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R-cadherin Influences Cell Motility via Rho Family GTPases^*

Emhonta Johnson, Christopher S. Theisen**, Keith R. Johnson¶||**, and Margaret J. Wheelock¶||**

From the Department of Oral Biology, College of Dentistry, Departments of Biochemistry and Molecular Biology, and ^¶Genetics, Cell Biology and Anatomy, and ^||Pathology and Microbiology, College of Medicine, ^**Eppley Institute for Research in Cancer and Allied Diseases, and Eppley Cancer Center, University of Nebraska Medical Center, Omaha, Nebraska 68198

Classical cadherins are the transmembrane proteins of the adherens junction and mediate cell-cell adhesion via homotypic interactions in the extracellular space. In addition, they mediate connections to the cytoskeleton by means of their association with catenins. Decreased cadherin-mediated adhesion has been implicated as an important component of tumorigenesis. Cadherin switching is central to the epithelial to mesenchymal transitions that drive normal developmental processes. Cadherin switching has also been implicated in tumorigenesis, particularly in metastasis. Recently, cadherins have been shown to be engaged in cellular activities other than adhesion, including motility, invasion, and signaling. In this study, we show that inappropriate expression of R-cadherin in tumor cells results in decreased expression of endogenous cadherins (cadherin switching) and sustained signaling through Rho GTPases. In addition, we show that R-cadherin induces cell motility when expressed in epithelial cells and that this increased motility is dependent upon Rho GTPase activity.

Received for publication, January 5, 2004 , and in revised form, April 20, 2004.

^* This work was supported by National Institutes of Health Grants R01-DE12308 (to K. R. J.), R01-GM51188 and P20-RR018759 (to M. J. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: University of Nebraska Medical Center 987696, Omaha, NE 68198-7696. Tel.: 402-559-3892; Fax: 402-559-3739; E-mail: mwheelock{at}unmc.edu.

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